Rational design of a prodrug to inhibit self-inflammation for cancer treatment

Photothermal therapy (PTT) has been extensively used as an effective therapeutic approach against cancer. However, PTT can trigger the proinflammatory response of dendritic cells (DCs) and macrophages to release proinflammatory cytokines, which can simulate tumor regeneration and further hinder subsequent therapy. Hence, an effective therapeutic system, comprising gold nanoparticle modified Cu₂ZnSnS₄ nanocrystals and aspirin (Au-CZTS/Asp), was developed to co-deliver PTT agents and inflammatory inhibitors for the synergistic treatment of cancer. Au-CZTS with high near infrared (NIR) photothermal conversion abilities can effectively induce apoptosis and tumor ablation under NIR light. Furthermore, Asp can inhibit the activation of the cGAS-STING pathway in DCs and the polarization of macrophages to intercept the PTT mediated inflammatory responses. Therefore, the as-prepared Au-CZTS/Asp can effectively realize the integration of tumor treatment and recovery. Simultaneously, the Au-CZTS/Asp with ultrasmall size can be rapidly cleared to reduce biotoxicity and side effects. In addition, the Au-CZTS/Asp showed excellent photoacoustic (PA) imaging properties around the tumor in vivo. Thus, our study provides a potential platform for a nano-prodrug that is viable for cancer diagnostic-treatment-recovery integration.